Prolactin (PRL) is a neuroendocrine polypeptide hormone primarily produced by the lactotrophs of the anterior pituitary gland in all vertebrates. Human prolactin (hPRL) is a 23 kDa protein that binds the prolactin receptor.
Human growth hormone (hGH) differs from human prolactin at about 25% of its residues. Wallis et al., supra. hGH participates in much of the regulation of normal human growth and development. This 22,000 dalton pituitary hormone regulates a multitude of biological effects including linear growth (somatogenesis), lactation, activation of macrophages, insulin-like effects and diabetagenic effects among others. See Chawla, R. K. (1983) Ann. Rev. Med. 34, 519; Edwards, C. K., et al. (1988) Science 239, 769; Thorner, M. O., et al. (1988) J. Clin. Invest. 81, 745.
In adults, the consequences of acquired GH deficiency include profound reduction in lean body mass and concomitant increase in total body fat, particularly in the truncal region. Decreased skeletal and cardiac muscle mass and muscle strength lead to a significant reduction in exercise capacity. Bone density is also reduced. Administration of exogenous growth hormone has been shown to reverse many of the metabolic changes. Additional benefits of therapy have included reduction in LDL cholesterol and improved psychological well-being.
To increase levels of growth hormone, exogenous growth hormone may be administered. Historically, the source of growth hormone had been the pituitary glands of cadavers. Extraction of growth hormone from this source, however, resulted in an expensive product that carried the risk of disease. Accordingly, this product has largely been displaced by recombinant growth hormone, thereby alleviating a risk of disease transmission, the product is still very expensive.
Accordingly, there is a need in the art for a more stable, longer acting growth hormone, that is equally or more effective than the growth hormone currently available in the art. A growth hormone with a longer serum half-life would off-set the frequency of growth hormone administration and therefore the expense associated with the growth hormone used in current treatment regimens.
Similarly, enhancing the stability of other ligands would also result in lower cost associated with exogenous hormone treatment.